Synchronous Fluorescence as a Sensor of Trace Amounts of Polycyclic Aromatic Hydrocarbons.

Synchronous fluorescence spectroscopy (SFS) is a technique that involves the simultaneous detection of fluorescence excitation and emission at a constant wavelength difference. The spectrum yields bands that are narrower and less complex than the original excitation and emission bands. The SFS bands correspond uniquely to the fluorescing molecule. Our investigation focuses on evaluating the sensitivity of the SFS technique for the detection and quantitation of PAHs relevant to astrochemistry. Results are presented for naphthalene, anthracene, and pyrene in three different solvents: n-hexane, water, and ethanol. SF bands are obtained with a constant wavelength difference between the peak excitation and emission wavelength (Δλ = λex - λem) at a concentration ranging from 10-4 to 10-10 M. Limit of detection (LOD) and limit of quantitation (LOQ) calculations are based on integrated SF band areas at different concentrations. Spectra of 23 pg/g of anthracene, 16 pg/g, and 2.6 pg/g of pyrene are recorded using ethanol as the solvent. The PAHs exhibit detection limits in the fractions of parts-per-billion (ng/g) range. Through comparison with similar prior studies employing fluorescence emission, our findings reveal a better detectability limit, demonstrating the effectiveness and applicability of the SFS technique.

Isocitrate dehydrogenase 2 inhibitor enasidenib synergizes daunorubicin cytotoxicity by targeting aldo-keto reductase 1C3 and ATP-binding cassette transporters.

Targeting mutations that trigger acute myeloid leukaemia (AML) has emerged as a refined therapeutic approach in recent years. Enasidenib (Idhifa) is the first selective inhibitor of mutated forms of isocitrate dehydrogenase 2 (IDH2) approved against relapsed/refractory AML. In addition to its use as monotherapy, a combination trial of enasidenib with standard intensive induction therapy (daunorubicin + cytarabine) is being evaluated. This study aimed to decipher enasidenib off-target molecular mechanisms involved in anthracycline resistance, such as reduction by carbonyl reducing enzymes (CREs) and drug efflux by ATP-binding cassette (ABC) transporters. We analysed the effect of enasidenib on daunorubicin (Daun) reduction by several recombinant CREs and different human cell lines expressing aldo-keto reductase 1C3 (AKR1C3) exogenously (HCT116) or endogenously (A549 and KG1a). Additionally, A431 cell models overexpressing ABCB1, ABCG2, or ABCC1 were employed to evaluate enasidenib modulation of Daun efflux. Furthermore, the potential synergism of enasidenib over Daun cytotoxicity was quantified amongst all the cell models. Enasidenib selectively inhibited AKR1C3-mediated inactivation of Daun in vitro and in cell lines expressing AKR1C3, as well as its extrusion by ABCB1, ABCG2, and ABCC1 transporters, thus synergizing Daun cytotoxicity to overcome resistance. This work provides in vitro evidence on enasidenib-mediated targeting of the anthracycline resistance actors AKR1C3 and ABC transporters under clinically achievable concentrations. Our findings may encourage its combination with intensive chemotherapy and even suggest that the effectiveness of enasidenib as monotherapy against AML could lie beyond the targeting of mIDH2.

Solar Desalination Using Thermally Responsive Ionic Liquids Regenerated with a Photonic Heater.

Growing global water demand has brought desalination technologies to the forefront for freshwater production from nontraditional water sources. Among these, forward osmosis (FO) is a promising two-step desalination process (draw dilution and regeneration), but it is often overlooked due to the energy requirements associated with draw regeneration. To address this limiting factor, we demonstrate FO desalination using thermally responsive ionic liquids (ILs) that are regenerated using a renewable energy input, that is, solar heat. To efficiently harness sunlight, a simple photonic heater converts incoming irradiation into infrared wavelengths that are directly absorbed by IL-water mixtures, thereby inducing phase separation to yield clean water. This approach is markedly different as it uses radiative heating, a noncontact mode of heat transfer that couples to chemical functional groups within the IL for rapid energy transfer without a heat exchanger or secondary fluid. Overall, a solar-thermal separation efficiency of 50% is achieved under unconcentrated sunlight, which can be increased to 69% with the thermal design. Successful desalination of produced water from oil wells in Southern California highlights the potential of solar-powered IL-FO for energy-efficient and low-cost desalination of complex brines for beneficial water reuse.

Interconnection of the Antenna Pigment 8-HDF and Flavin Facilitates Red-Light Reception in a Bifunctional Animal-like Cryptochrome.

Cryptochromes are ubiquitous flavin-binding light sensors closely related to DNA-repairing photolyases. The animal-like cryptochrome CraCRY from the green alga Chlamydomonas reinhardtii challenges the paradigm of cryptochromes as pure blue-light receptors by acting as a (6-4) photolyase, using 8-hydroxy-5-deazaflavin (8-HDF) as a light-harvesting antenna with a 17.4 Šdistance to flavin and showing spectral sensitivity up to 680 nm. The expanded action spectrum is attributed to the presence of the flavin neutral radical (FADH•) in the dark, despite a rapid FADH• decay observed in vitro in samples exclusively carrying flavin. Herein, the red-light response of CraCRY carrying flavin and 8-HDF was studied, revealing a 3-fold prolongation of the FADH• lifetime in the presence of 8-HDF. Millisecond time-resolved ultraviolet-visible spectroscopy showed the red-light-induced formation and decay of an absorbance band at 458 nm concomitant with flavin reduction. Time-resolved Fourier transform infrared (FTIR) spectroscopy and density functional theory attributed these changes to the deprotonation of 8-HDF, challenging the paradigm of 8-HDF being permanently deprotonated in photolyases. FTIR spectra showed changes in the hydrogen bonding network of asparagine 395, a residue suggested to indirectly control flavin protonation, indicating the involvement of N395 in the stabilization of FADH•. Fluorescence spectroscopy revealed a decrease in the energy transfer efficiency of 8-HDF upon flavin reduction, possibly linked to 8-HDF deprotonation. The discovery of the interdependence of flavin and 8-HDF beyond energy transfer processes highlights the essential role of the antenna, introducing a new concept enabling CraCRY and possibly other bifunctional cryptochromes to fulfill their dual function.

Hepatic Mitochondrial Defects in a Nonalcoholic Fatty Liver Disease Mouse Model Are Associated with Increased Degradation of Oxidative Phosphorylation Subunits.

Nonalcoholic fatty liver disease (NAFLD) is associated with hepatic mitochondrial dysfunction characterized by reduced ATP synthesis. We applied the 2H2O-metabolic labeling approach to test the hypothesis that the reduced stability of oxidative phosphorylation proteins contributes to mitochondrial dysfunction in a diet-induced mouse model of NAFLD. A high fat diet containing cholesterol (a so-called Western diet (WD)) led to hepatic oxidative stress, steatosis, inflammation and mild fibrosis, all markers of NAFLD, in low density cholesterol (LDL) receptor deficient (LDLR-/-) mice. In addition, compared with controls (LDLR-/- mice on normal diet), livers from NAFLD mice had reduced citrate synthase activity and ATP content, suggesting mitochondrial impairment. Proteome dynamics study revealed that mitochondrial defects are associated with reduced average half-lives of mitochondrial proteins in NAFLD mice (5.41 ± 0.46 versus 5.15 ± 0.49 day, p < 0.05). In particular, the WD reduced stability of oxidative phosphorylation subunits, including cytochrome b-c1 complex subunit 1 (5.9 ± 0.1 versus 3.4 ± 0.8 day), ATP synthase subunit α (6.3 ± 0.4 versus 5.5 ± 0.4 day) and ATP synthase F(0) complex subunit B1 of complex V (8.5 ± 0.6 versus 6.5 ± 0.2 day) (p < 0.05). These changes were associated with impaired complex III and F0F1-ATP synthase activities. Markers of mitophagy were increased, but proteasomal degradation activity were reduced in NAFLD mice liver, suggesting that ATP deficiency because of reduced stability of oxidative phosphorylation complex subunits contributed to inhibition of ubiquitin-proteasome and activation of mitophagy. In conclusion, the 2H2O-metabolic labeling approach shows that increased degradation of hepatic oxidative phosphorylation subunits contributed to mitochondrial impairment in NAFLD mice.

Calculation of the Protein Turnover Rate Using the Number of Incorporated 2H Atoms and Proteomics Analysis of a Single Labeled Sample.

Rate constant estimation with heavy water requires a long-term experiment with data collection at multiple time points (3-4 weeks for mitochondrial proteome dynamics in mice and much longer in other species). When tissue proteins are analyzed, this approach requires euthanizing animals at each time point or multiple tissue biopsies in humans. Although short-term protocols are available, they require knowledge of the maximum number of isotope labels (N) and accurate quantification of observed 2H-enrichment in the peptide. The high-resolution accurate mass spectrometers used for proteome dynamics studies are characterized by a systematic spectral error that compromises these measurements. To circumvent these issues, we developed a simple algorithm for the rate constant calculation based on a single labeled sample and comparable unlabeled (time 0) sample. The algorithm determines N for all proteogenic amino acids from a long-term experiment to calculate the predicted plateau 2H-labeling of peptides for a short-term protocol and estimates the rate constant based on the measured baseline and the predicted plateau 2H-labeling of peptides. The method was validated based on the rate constant estimation in a long-term experiment in mice and dogs. The improved 2 time-point method enables the rate constant calculation with less than 10% relative error compared to the bench-marked multi-point method in mice and dogs and allows us to detect diet-induced subtle changes in ApoAI turnover in mice. In conclusion, we have developed and validated a new algorithm for protein rate constant calculation based on 2-time point measurements that could also be applied to other biomolecules.

Maternal ornithine transcarbamylase deficiency, a genetic condition associated with high maternal and neonatal mortality every clinician should know: A systematic review.

Ornithine transcarbamylase deficiency (OTCD) is a rare X-linked urea cycle disorder. Maternal OTCD can lead to life-threatening hyperammonemia if untreated. We aimed to compare the outcomes of maternal OTCD when diagnosis is known prior to pregnancy to when diagnosis is made during pregnancy. We performed a systematic literature review on maternal OTCD using the databases Ovid MEDLINE and PubMed from 1982 through 2018. Studies were included if addressed maternal OTCD signs, symptoms, and detailed pregnancy outcomes. We calculated the median or the mean for continuous variables and percentages for categorical variables. Of 36 cases of maternal OTCD, 20 (55%) were diagnosed prior to pregnancy while 16 (45%) were not. In the 20 patients diagnosed prior to pregnancy, 7 (35%) had either a neurologic or psychiatric presentation during pregnancy or postpartum. Two hyperammonemic patients (11%) experienced ICU admission, dialysis, and coma with no maternal deaths. All had a favorable outcome. In the 16 patients not known to have maternal OTCD prior to pregnancy, 13 (81%) had neurologic or psychiatric presentation during pregnancy or postpartum. Four presented with hyperemesis gravidarum. Eleven (69%) hyperammonemic patients had ICU admission and coma and 7 (47%) of them had dialysis. There were 5 (31%) maternal deaths. Three patients (19%) had prolonged hospitalization course. Overall, three male neonatal deaths were reported. Three other male children had liver transplant. Maternal OTCD is associated with high maternal and neonatal morbidity and mortality when diagnosis is made during pregnancy compared to when diagnosis is known prior to pregnancy.

Metal-Assisted Ligand-Centered Electrocatalytic Hydrogen Evolution upon Reduction of a Bis(thiosemicarbazonato)Cu(II) Complex.

In this study, we report the electrocatalytic behavior of the neutral, monomeric Cu(II) complex of diacetyl-bis(N-4-methyl-3-thiosemicarbazonato), CuL1, for metal-assisted ligand-centered hydrogen evolution in acetonitrile and dimethylformamide. CuL1 displays a maximum turnover frequency (TOF) of 10 000 s-1 in acetonitrile and 5100 s-1 in dimethylformamide at an overpotential of 0.80 and 0.76 V, respectively. The rate law is first-order in catalyst and second-order in proton concentration. Gas analysis from controlled potential electrolysis confirms CuL1 as an electrocatalyst to produce H2 with a minimum Faradaic efficiency of 81% and turnover numbers as high as 73 while showing no sign of degradation over 23 h. The H2 evolution reaction (HER) was probed using deuterated acid, demonstrating a kinetic isotope effect of 7.54. A proton inventory study suggests one proton is involved in the rate-determining step. Catalytic intermediates were identified using 1H NMR, X-ray photoelectron, and UV-visible spectroscopies. All catalytic intermediates in the proposed mechanism were successfully optimized using density functional theory calculations with the B3LYP functional and the 6-311g(d,p) basis set and support the proposed mechanism.

Translation of Ligand-Centered Hydrogen Evolution Reaction Activity and Mechanism of a Rhenium-Thiolate from Solution to Modified Electrodes: A Combined Experimental and Density Functional Theory Study.

The homogeneous, nonaqueous catalytic activity of the rhenium-thiolate complex ReL3 (L = diphenylphosphinobenzenethiolate) for the hydrogen evolution reaction (HER) has been transferred from nonaqueous homogeneous to aqueous heterogeneous conditions by immobilization on a glassy carbon electrode surface. A series of modified electrodes based on ReL3 and its oxidized precursor [ReL3][PF6] were fabricated by drop-cast methods, yielding catalytically active species with HER overpotentials for a current density of 10 mA/cm2, ranging from 357 to 919 mV. The overpotential correlates with film resistance as measured by electrochemical impedance spectroscopy and film morphology as determined by scanning and transmission electron microscopy. The lowest overpotential was for films based on the ionic [ReL3][PF6] precursor with the inclusion of carbon black. Stability measurements indicate a 2 to 3 h conditioning period in which the overpotential increases, after which no change in activity is observed within 24 h or upon reimmersion in fresh aqueous, acidic solution. Electronic spectroscopy results are consistent with ReL3 as the active species on the electrode surface; however, the presence of an undetected quantity of catalytically active degradation species cannot be excluded. The HER mechanism was evaluated by Tafel slope analysis, which is consistent with a novel Volmer-Heyrovsky-Tafel-like mechanism that parallels the proposed homogeneous HER pathway. Proposed mechanisms involving traditional metal-hydride processes vs ligand-centered reactivity were examined by density functional theory, including identification and characterization of relevant transition states. The ligand-centered path is energetically favored with protonation of cis-sulfur sites culminating in homolytic S-H bond cleavage with H2 evolution via H atom coupling.

Beyond Metal-Hydrides: Non-Transition-Metal and Metal-Free Ligand-Centered Electrocatalytic Hydrogen Evolution and Hydrogen Oxidation.

A new pathway for homogeneous electrocatalytic H2 evolution and H2 oxidation has been developed using a redox active thiosemicarbazone and its zinc complex as seminal metal-free and transition-metal-free examples. Diacetyl-bis(N-4-methyl-3-thiosemicarbazone) and zinc diacetyl-bis(N-4-methyl-3-thiosemicarbazide) display the highest reported TOFs of any homogeneous ligand-centered H2 evolution catalyst, 1320 and 1170 s(-1), respectively, while the zinc complex also displays one of the highest reported TOF values for H2 oxidation, 72 s(-1), of any homogeneous catalyst. Catalysis proceeds via ligand-centered proton-transfer and electron-transfer events while avoiding traditional metal-hydride intermediates. The unique mechanism is consistent with electrochemical results and is further supported by density functional theory. The results identify a new direction for the design of electrocatalysts for H2 evolution and H2 oxidation that are not reliant on metal-hydride intermediates.

Proposed Ligand-Centered Electrocatalytic Hydrogen Evolution and Hydrogen Oxidation at a Noninnocent Mononuclear Metal-Thiolate.

The noninnocent coordinatively saturated mononuclear metal-thiolate complex ReL3 (L = diphenylphosphinobenzenethiolate) serves as an electrocatalyst for hydrogen evolution or hydrogen oxidation dependent on the presence of acid or base and the applied potential. ReL3 reduces acids to H2 in dichloromethane with an overpotential of 380 mV and a turnover frequency of 32 ± 3 s(-1). The rate law displays a second-order dependence on acid concentration and a first-order dependence on catalyst concentration with an overall third-order rate constant (k) of 184 ± 2 M(-2) s(-1). Reactions with deuterated acid display a kinetic isotope effect of 9 ± 1. In the presence of base, ReL3 oxidizes H2 with a turnover frequency of 4 ± 1 s(-1). The X-ray crystal structure of the monoprotonated species [Re(LH)L2](+), an intermediate in both catalytic H2 evolution and oxidation, has been determined. A ligand-centered mechanism, which does not require metal hydride intermediates, is suggested based on similarities to the redox-regulated, ligand-centered binding of ethylene to ReL3.

Oxygen Transport through Amorphous Cathode Coatings in Solid-State Batteries.

All solid-state batteries (SSBs) are considered the most promising path to enabling higher energy-density portable energy, while concurrently improving safety as compared to current liquid electrolyte solutions. However, the desire for high energy necessitates the choice of high-voltage cathodes, such as nickel-rich layered oxides, where degradation phenomena related to oxygen loss and structural densification at the cathode surface are known to significantly compromise the cycle and thermal stability. In this work, we show, for the first time, that even in an SSB, and when protected by an intact amorphous coating, the LiNi0.5Mn0.3Co0.2O2 (NMC532) surface transforms from a layered structure into a rocksalt-like structure after electrochemical cycling. The transformation of the surface structure of the Li3B11O18 (LBO)-coated NMC532 cathode in a thiophosphate-based solid-state cell is characterized by high-resolution complementary electron microscopy techniques and electron energy loss spectroscopy. Ab initio molecular dynamics corroborate facile transport of O2- in the LBO coating and in other typical coating materials. This work identifies that oxygen loss remains a formidable challenge and barrier to long-cycle life high-energy storage, even in SSBs with durable, amorphous cathode coatings, and directs attention to considering oxygen permeability as an important new design criteria for coating materials.

Updated DPYD HapB3 haplotype structure and implications for pharmacogenomic testing.

The DPYD gene encodes dihydropyrimidine dehydrogenase, the rate-limiting enzyme for the metabolism of fluoropyrimidines 5-fluorouracil and capecitabine. Genetic variants in DPYD have been associated with altered enzyme activity, therefore accurate detection and interpretation is critical to predict metabolizer status for individualized fluoropyrimidine therapy. The most commonly observed deleterious variation is the causal variant linked to the previously described HapB3 haplotype, c.1129-5923C>G (rs75017182) in intron 10, which introduces a cryptic splice site. A benign synonymous variant in exon 11, c.1236G>A (rs56038477) is also linked to HapB3 and is commonly used for testing. Previously, these single-nucleotide polymorphisms (SNPs) have been reported to be in perfect linkage disequilibrium (LD); therefore, c.1236G>A is often utilized as a proxy for the function-altering intronic variant. Clinical genotyping of DPYD identified a patient who had c.1236G>A, but not c.1129-5923C>G, suggesting that these two SNPs may not be in perfect LD, as previously assumed. Additional individuals with c.1236G>A, but not c.1129-5923C>G, were identified in the Children's Mercy Data Warehouse and the All of Us Research Program version 7 cohort substantiating incomplete SNP linkage. Consequently, testing only c.1236G>A can generate false-positive results in some cases and lead to suboptimal dosing that may negatively impact patient therapy and prospect of survival. Our data show that DPYD genotyping should include the functional variant c.1129-5923C>G, and not the c.1236G>A proxy, to accurately predict DPD activity.

Frequency of pharmacogenomic variation and medication exposures among All of Us Participants.

Pharmacogenomics promises improved outcomes through individualized prescribing. However, the lack of diversity in studies impedes clinical translation and equitable application of precision medicine. We evaluated the frequencies of PGx variants, predicted phenotypes, and medication exposures using whole genome sequencing and EHR data from nearly 100k diverse All of Us Research Program participants. We report 100% of participants carried at least one pharmacogenomics variant and nearly all (99.13%) had a predicted phenotype with prescribing recommendations. Clinical impact was high with over 20% having both an actionable phenotype and a prior exposure to an impacted medication with pharmacogenomic prescribing guidance. Importantly, we also report hundreds of alleles and predicted phenotypes that deviate from known frequencies and/or were previously unreported, including within admixed American and African ancestry groups.

The frequency of pathogenic variation in the All of Us cohort reveals ancestry-driven disparities.

Disparities in data underlying clinical genomic interpretation is an acknowledged problem, but there is a paucity of data demonstrating it. The All of Us Research Program is collecting data including whole-genome sequences, health records, and surveys for at least a million participants with diverse ancestry and access to healthcare, representing one of the largest biomedical research repositories of its kind. Here, we examine pathogenic and likely pathogenic variants that were identified in the All of Us cohort. The European ancestry subgroup showed the highest overall rate of pathogenic variation, with 2.26% of participants having a pathogenic variant. Other ancestry groups had lower rates of pathogenic variation, including 1.62% for the African ancestry group and 1.32% in the Latino/Admixed American ancestry group. Pathogenic variants were most frequently observed in genes related to Breast/Ovarian Cancer or Hypercholesterolemia. Variant frequencies in many genes were consistent with the data from the public gnomAD database, with some notable exceptions resolved using gnomAD subsets. Differences in pathogenic variant frequency observed between ancestral groups generally indicate biases of ascertainment of knowledge about those variants, but some deviations may be indicative of differences in disease prevalence. This work will allow targeted precision medicine efforts at revealed disparities.

Evaluation of Early Screening for Diabetes Mellitus in Pregnancy with Hemoglobin A1c.

Early diabetes screening is recommended for high-risk pregnant women risk via a 1-hour glucose challenge test (1-hour GCT). Hemoglobin A1c (HbA1c) can be obtained with initial obstetric laboratories. We sought to examine the relationship between HbA1c and 1-hour GCT for early diabetes screening in pregnancy. This is a retrospective cohort study of 204 high-risk pregnant women who underwent early HbA1c and 1-hour GCT. Simple logistic regression analysis was performed to predict abnormal 1-hour GCT and diagnosis of diabetes using HbA1c. A total of 158 (77.5%), 44 (21.5%), and 2 (1%) women had HbA1c of less than 5.7, 5.7 to 6.4, and 6.5% or higher, respectively. Seven of 158 (4.4%) women with HbA1c less than 5.7% and 8 of 44 (18.2%) with HbA1c of 5.7 to 6.4% had a diagnosis of diabetes. A positive correlation between early HbA1c and 1-hour GCT was detected. Logistic regression showed HbA1c significantly predicted the risk of diabetes but was not a good predictor of abnormal 1-hour GCT. HbA1c of 5.5% or less had a 97% or higher negative predictive value for early diabetes in pregnancy. There is a positive correlation between HbA1c and 1-hour GCT for the early screening of diabetes in pregnancy. Women with early HbA1c ≤ 5.5% could forego further testing in early pregnancy.

MicroRNA analysis in maternal blood of pregnancies with preterm premature rupture of membranes reveals a distinct expression profile.

OBJECTIVE: To determine the expression profile of microRNAs in the peripheral blood of pregnant women with preterm premature rupture of membranes (PPROM) compared to that of healthy pregnant women. STUDY DESIGN: This was a pilot study with case-control design in pregnant patients enrolled between January 2017 and June 2019. Patients with healthy pregnancies and those affected by PPROM between 20- and 33+6 weeks of gestation were matched by gestational age and selected for inclusion to the study. Patients were excluded for multiple gestation and presence of a major obstetrical complication such as preeclampsia, diabetes, fetal growth restriction and stillbirth. A total of ten (n = 10) controls and ten (n = 10) patients with PPROM were enrolled in the study. Specimens were obtained before administration of betamethasone or intravenous antibiotics. MicroRNA expression was analyzed for 800 microRNAs in each sample using the NanoString nCounter Expression Assay. Differential expression was calculated after normalization and log2- transformation using the false discovery rate (FDR) method at an alpha level of 5%. RESULTS: Demographic characteristics were similar between the two groups. Of the 800 miRNAs analyzed, 116 were differentially expressed after normalization. However, only four reached FDR-adjusted statistical significance. Pregnancies affected by PPROM were characterized by upregulation of miR-199a-5p, miR-130a-3p and miR-26a-5p and downregulation of miR-513b-5p (FDR adjusted p-values <0.05). The differentially expressed microRNAs participate in pathways associated with altered collagen and matrix metalloprotease expression in the extracellular matrix. CONCLUSION: Patients with PPROM have a distinct peripheral blood microRNA profile compared to healthy pregnancies as measured by the NanoString Expression Assay.

Brackish water desalination using reverse osmosis and capacitive deionization at the water-energy nexus.

In this article, we present a critical review of the reported performance of reverse osmosis (RO) and capacitive deionization (CDI) for brackish water (salinity < 5.0 g/L) desalination from the aspects of engineering, energy, economy and environment. We first illustrate the criteria and the key performance indicators to evaluate the performance of brackish water desalination. We then systematically summarize technological information of RO and CDI, focusing on the effect of key parameters on desalination performance, as well as energy-water efficiency, economic costs and environmental impacts (including carbon footprint). We provide in-depth discussion on the interconnectivity between desalination and energy, and the trade-off between kinetics and energetics for RO and CDI as critical factors for comparison. We also critique the results of technical-economic assessment for RO and CDI plants in the context of large-scale deployment, with focus on lifetime-oriented consideration to total costs, balance between energy efficiency and clean water production, and pretreatment/post-treatment requirements. Finally, we illustrate the challenges and opportunities for future brackish water desalination, including hybridization for energy-efficient brackish water desalination, co-removal of specific components in brackish water, and sustainable brine management with innovative utilization. Our study reveals that both RO and CDI should play important roles in water reclamation and resource recovery from brackish water, especially for inland cities or rural regions.